Trifluoroacetic acid → 2-[1-(1-Cyclopropylmethyl-cyclopropanesulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-4-(7-methoxy-2-pyridin-2-yl-quinolin-4-yloxy)-pyrrolidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1815720Notes

Reaction equation

HRID 1815720 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:15]=2)[CH2:10][CH:9]1[C:32]([OH:34])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:38]([CH:41]([CH3:43])[CH3:42])CC)(C)C.C(O)(C(F)(F)F)=[O:45].NC1(C([NH:59][S:60]([C:63]2([CH2:66][CH:67]3[CH2:69][CH2:68]3)[CH2:65][CH2:64]2)(=[O:62])=[O:61])=O)CC1C=C.[CH:70]1[CH:71]=CC2N(O)N=NC=2[CH:75]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:15]=2)[CH2:10][CH:9]1[C:32](=[O:34])[NH:38][C:41]1([C:42]([NH:59][S:60]([C:63]2([CH2:66][CH:67]3[CH2:69][CH2:68]3)[CH2:64][CH2:65]2)(=[O:61])=[O:62])=[O:45])[CH2:43][CH:71]1[CH:70]=[CH2:75])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 207736124-(7-Methoxy-2-pyridin-2-yl-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic Acid 1-tert-butyl EsterHCID 86591863HCID 86591863, compound

Product 1

HCID 207736632-[1-(1-Cyclopropylmethyl-cyclopropanesulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-4-(7-methoxy-2-pyridin-2-yl-quinolin-4-yloxy)-pyrrolidine-1-carboxylic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step 78e) To a mixture of the acid (0.33 g, 0.71 mmol) of the product of Step 78d (Example 78), diisopropylethylamine (0.5 mL, 3.6 mmol), TFA salt (0.205 g, 0.51 mmol) of 1-Cyclopropylmethyl-cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropanecarbonyl)-amide, and HOBt (0.1 g, 0.6 mmol) in CH2Cl2 (8 mL) was added HATU (0.35 g, 0.92 mmol). The reaction mixture was stirred at rt overnite and diluted with EtOAc, washed with pH 4.0 buffer, dried (MgSO4), removed the solvent in vacuo. The residue was purified by PTLC to provide the product in 59% (0.22 g) yield: 1H NMR (methanol-d4) □ ppm 0.64 (m, 1H), 0.96 (m, 2H), 1.33 (m, 8H), 1.39 (m, 9H), 1.90 (m, 2H), 2.18 (m, 1H), 2.54 (m, 1H), 2.81 (m, 1H), 4.01 (m, 5H), 4.44 (d, J=28.99 Hz, 1H), 5.08 (m, 1H), 5.31 (m, 1H), 5.57 (s, 1H), 6.03 (m, 1H), 6.94 (s, t H), 7.27 (d, J=8.24 Hz, 1H), 7.64 (m, 1H), 7.92 (m, 1H), 8.14 (m, 2H), 8.66 (s, 1H), 8.74 (s, 1H).

Workup

  1. washwashed with pH 4.0 buffer
  2. dry with materialdried (MgSO4)
  3. customremoved the solvent in vacuo
  4. customThe residue was purified by PTLC
  5. customto provide the product in 59% (0.22 g) yield

Sources & evidence

ORD record
ord-519c7384640448d1806fc4b92bc256fb
Source dataset
uspto-grants-2005_04
Patent number
US06878722B2

Reaction notes

Loading…